Vitamin D Insufficiency Linked to Asthma Severity
asthma inhalersVitamin D insufficiency is linked to asthma severity, according to the results of a cross-sectional study reported in the May 1 issue of the American Journal of Respiratory and Critical Care Medicine.

"Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood," write Erick Forno, from Brigham and Women's Hospital in Boston, Massachusetts, and colleagues. "However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood."

The goal of this study was to evaluate the association between measured levels of 25-hydroxyvitamin D ([25(OH)D]; the predominant circulating form of vitamin D) and markers of asthma severity and allergy in 616 Costa Rican children aged 6 to 14 years. Univariate and multivariate analyses were performed with use of linear, logistic, and negative binomial regressions. Increased airway responsiveness was defined as a 8.58-µmol or less provocative dose of methacholine producing a 20% decrease in baseline forced expiratory volume in 1 second.

Levels of vitamin D were insufficient (< 30 ng/mL) in 175 (28%) of 616 children with asthma. Vitamin D levels were significantly and inversely associated with total immunoglobulin E (IgE) and eosinophil count, based on multivariate linear regression models. A log10-unit increase in vitamin D levels was associated with lower odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004 - 0.71; P = .03), any use of anti-inflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05 - 0.67; P = .01), and increased airway responsiveness (OR, 0.15; 95% CI, 0.024 - 0.97; P = .05), according to multivariate logistic regression models.

"Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma," the study authors write. "In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity."

Limitations of this study include debate regarding what constitutes a normal circulating vitamin D level, lack of a control group, cross-sectional design, and possible residual confounding by socioeconomic status.

"Our data suggest that additional work needs to be done to determine the potential beneficial role that vitamin D might play, if any, in established human allergy and asthma," the study authors conclude. "These studies should include in vitro and animal studies to further elucidate the mechanisms for the role of vitamin D, and eventual clinical trials of vitamin D supplementation to prevent exacerbations. In addition, common polymorphisms in the vitamin D receptor and other genes in the vitamin D pathway should be further characterized, especially as they relate to circulating vitamin D levels and asthma severity."

In an accompanying editorial, Graham Devereux, MD, from the University of Aberdeen in Aberdeen, United Kingdom, and colleagues discuss the difficult scientific, ethical, and regulatory issues involved in intervention studies of vitamin D in the primary prevention and treatment of asthma.

"Studies that supplement with the currently recommended doses of vitamin D, while unlikely to raise ethical or regulatory concerns, would fail to address the scientific evidence that larger vitamin D intakes (e.g., 2,000 IU/d) may be required for beneficial nonskeletal effects," the editorialists write. "While these concerns may be satisfactorily addressed, it remains to be seen whether pregnant women, parents, or patients will be similarly convinced and participate in such studies. Ultimately, it is only by investigating the effects of vitamin D in doses at, and above those currently recommended, that decisions can be made on the optimal intake of vitamin D for health and the possible prevention and treatment of asthma."

The National Institutes of Health supported this study. One of the study authors has been a consultant to DiaSorin Corporation. Another study author has disclosed various financial and/or other relationships with AstraZeneca, Boehringer Ingelheim, Genentech, Glaxo-Wellcome, Roche Pharmaceuticals, Pfizer, Schering Plough, Variagenics, Genome Therapeutics, and Merck Frost. The editorialists have disclosed no relevant financial relationships.

Am J Respir Crit Care Med. 2009;179:739-742, 765-771.

Clinical Context

Vitamin D has significant effects on immune function, and an editorial by Devereux and colleagues, which accompanies the current article, reviews the metabolism of vitamin D. Humans obtain approximately 90% of their vitamin D through sunlight, with the remainder coming from diet. Despite this fact, research has demonstrated that more than half of individuals in places with high exposure to sunshine, such as Hawaii, still have evidence of vitamin D deficiency. Foods with significant levels of naturally occurring vitamin D are limited to oily fish and egg yolk, although dairy products are often fortified with vitamin D.

Observational studies regarding the effects of vitamin D on asthma and allergy have yielded mixed results. The current study examines the effects of vitamin D on disease markers in asthmatic children.

Study Highlights

  • Study participants were Costa Rican children between the ages of 6 and 14 years with asthma. All children completed questionnaires regarding asthma severity, as well as pulmonary function testing, methacholine challenge testing, allergy skin testing, and measurement of total and allergen-specific serum IgE as well as peripheral blood eosinophils.
  • The main outcome of the study was the relationship between these outcomes and serum levels of 25(OH)D. Vitamin D deficiency was defined as levels of 25(OH)D less than 20 ng/mL, and levels between 20 and 30 ng/mL indicated insufficient vitamin D.
  • Researchers adjusted the study results to account for potential confounders, including age, sex, parental educational levels, and body mass index.
  • 616 children provided study data. The mean age was 8.7 years, and 40% of participants were girls. Elevated total IgE levels, increased eosinophil count, and skin test reactivity were common findings among this cohort, and 91% of children had experienced an unscheduled medical visit for asthma in the past year. Despite this, only 39% had received an anti-inflammatory medication in the last year.
  • 3.4% of participants had vitamin D deficiency, and another 24.6% were considered to have an insufficient amount of vitamin D.
  • 25(OH)D levels were inversely related to total IgE and eosinophil levels. For each 10-ng/mL increase in 25(OH)D levels in an average male subject, serum total IgE levels and eosinophil counts fell by 25 IU/mL and 29 cells/m3, respectively.
  • Vitamin D levels also were inversely related to the size of skin test reactivity to dust mites.
  • Higher vitamin D levels predicted less airway hyperresponsiveness on methacholine challenge tests, but there was no independent effect of 25(OH)D levels on the mean forced expiratory volume in 1 second.
  • Finally, vitamin D levels were inversely associated with the risk for hospitalization for asthma in the previous year.
  • In full confirmatory analysis, vitamin D levels were unrelated to the use of anti-inflammatory medications.

Clinical Implications

  • Approximately 90% of vitamin D in humans is derived from the sun, but many individuals in sunny areas still have vitamin D deficiency. Vitamin D is found in oily fish and egg yolks, and it has been demonstrated to have immunomodulating effects.
  • The current study of asthmatic children demonstrates that serum vitamin D levels are inversely related to serum total IgE levels and eosinophilia counts, airway hyperresponsiveness, and hospital admissions for asthma. However, vitamin D levels were unrelated to the mean forced expiratory volume in 1 second.
News Author: Laurie Barclay, MD; CME Author: Charles Vega, MD, FAA

May 4, 2009

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